Lipidanker

Lipidanker, commonly referred to as a lipid anchor, is a covalently attached lipid group that tethers a protein to a cellular membrane. This modification enables peripheral proteins to associate with membranes, influences signaling pathways, and can determine protein localization within different cellular compartments.

Several distinct lipid anchors exist. N-terminal acylation attaches myristoyl or palmitoyl groups to proteins, often involving N-myristoyltransferase or palmitoyltransferases. C-terminal prenylation attaches farnesyl or geranylgeranyl groups to a cysteine in a CaaX motif via prenyltransferases. A GPI anchor attaches a protein to a glycosylphosphatidylinositol moiety in the endoplasmic reticulum, releasing a GPI-anchored protein to the outer leaflet. Lipid anchors can be dynamically regulated; palmitoylation is frequently reversible, allowing cycles of membrane association and cytosolic dispersion.

Functional roles include targeting signaling proteins such as small GTPases and kinases to membranes, affecting interaction networks and activity. Classic examples include Ras family proteins with prenylation and, in some cases, palmitoylation, and Src-family kinases that rely on acylation for membrane targeting. GPI-anchored proteins, such as CD55, lack transmembrane domains and instead attach to the membrane via GPI anchors.

Biosynthesis occurs through specific enzyme cascades in the endoplasmic reticulum or cytosol, and synthetic lipid anchors are used experimentally to localize peptides to membranes or to alter pharmacokinetics. Lipidanker concepts are widely used in cell biology, biochemistry, and drug development to understand how membrane localization shapes protein function.